ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Tumor treatment-related adverse reactions are a major focus of clinical concern， among which recurrent aphthous oral ulcers （RAU） associated with targeted therapy for lung cancer （LC） are among the most painful and distressing for patients. Currently， modern medical interventions show limited efficacy， and there is an urgent need for more effective treatment strategies. This study differentiates RAU associated with targeted therapy for LC from chemotherapy-related and ordinary oral ulcers， elucidates the pathophysiological basis of such ulcers， and traces the theoretical origin of "Yin deficiency and Qi collapse". Based on the new system of "five perspectives on diagnosis and treatment" for tumor prevention and treatment， with a focus on the core and symptom perspectives and rooted in the traditional concept of "lung dominating Qi"， we innovatively propose the concept of "medicine-induced ulcer" and are the first to introduce the theory of "Yin deficiency and Qi collapse" into the syndrome differentiation and treatment of RAU associated with targeted therapy for LC （i.e.， medicine-induced ulcer）. We propose that "Yin deficiency and Qi collapse" is the core pathogenesis of medicine-induced ulcers， in which the collapse of formless Qi is the key to their onset， while the deficiency and stasis of tangible Yin and blood constitute the root of recurrence. A hierarchical strategy for syndrome differentiation and treatment is established： first treating the collapse of formless Qi， then replenishing tangible deficiencies， and concurrently preventing recurrence. We emphasize that treatment should address both root and manifestation， with appropriate prioritization. In the acute phase， while relieving symptoms and promoting ulcer healing by nourishing Qi， uplifting collapse， and generating body fluids， attention should also be paid to nourishing spleen Yin， facilitating the circulation of nutritive Qi， and alleviating stasis to target the root pathogenesis and reduce recurrence. A verified case is presented to support this approach. This study enriches the theoretical framework and clinical methods of traditional Chinese medicine （TCM） in the treatment of RAU associated with targeted therapy for LC， promotes symptom management of treatment-related adverse reactions through integrated TCM and Western medicine， and provides theoretical support for the construction and development of a comprehensive differentiation and treatment system for lung cancer prevention， treatment， and rehabilitation.

Objective To analyze the spatial and temporal distribution characteristics of hand-foot-mouth disease (HFMD) in Zibo City, to explore the key incidence areas, and to find a suitable prediction model, so as to provide reference for the prevention and control of HFMD. Methods The spatiotemporal clustering characteristics of HFMD in Zibo City from 2018 to 2023 were analyzed by using SaTScan 10.0.2 software and ArcGIS 10.7 software. A combination model of ARIMA and SVM was established, and the prediction results were verified and compared. Results Spatial clustering analysis showed that there was spatial clustering of the incidence of HFMD in various townships of Zibo City from 2020 to 2022. The high-high clustering areas and Getis-Ord hot spot areas were mainly concentrated in some main urban areas of Zhangdian District, Zichuan District, and Huantai County. A total of 2-5 aggregation areas were detected by spatiotemporal scanning analysis. The first-type aggregation areas were mainly concentrated in the towns of Zhangdian District, Huantai County, Linzi District, Zhoucun District and Gaoxin District. The aggregation months were July, August, September and November. The model prediction results showed that the ARIMA-SVM combined model was more accurate than the traditional ARIMA model. Conclusion There is a spatiotemporal clustering of hand-foot-mouth disease in Zibo City. The ARIMA-SVM combined model can be used to predict the incidence of hand-foot-mouth disease in Zibo City, and to strengthen health education and disease monitoring in high-risk areas and populations during the epidemic months.

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.

On September 3,2020,the U.S.Food and Drug Administration(FDA)granted formal approval to Copper Cu 64 dotatate(commercially known as Detectnet),for its pivotal role in diagnosing somatostatin receptor(SSTR)positive neuroendocrine tumors(NETs)in adult patients.This innovative diagnostic agent,Copper Cu 64 dotatate,is a sophisticated radionuclide that selectively targets somatostatin receptors,facilitating the emission of positron(β+)radionuclides in a quantity conducive for high-resolution positron emission tomography(PET)imaging.This review delves into the intricate mechanisms of action,the dynamic pharmacokinetics,comprehensive clinical studies,and the safety profile of Copper Cu 64 dotatate,highlighting its significance in the realm of medical diagnostics.

Objective To study the effects of hesperidin on the migration ability of human keratinocytes(HaCaT)and human skin fibroblasts(HSF).Additionally,this research aims to preliminary investigate the influence and underlying mechanism of Hesperidin in facilitating the healing process of acute skin wounds in mice.Methods HaCaT and HSF were divided into blank group(without any treatment),control group(added 0.1％dimethyl sulfoxide)and experimental group(added 5.0 μg·mL-1 hesperidin)for 48 h.The healing ability of cells in vitro was detected by scratch test.The migration of cells was detected by Transwell migration test.C57 mice were randomly divided into model group,experimental-L,-H groups.The acute full-thickness skin defect wound model was established by surgical clipping of the full-thickness skin of the back of mice.The model group was given 0.5％dimethyl sulfoxide,and the experimental-L,-H groups were given 10,50 mg·kg-1 hesperidin solution,respectively.The protein expressions levels of β-catenin,proliferating cell nuclear antigen(PCNA),keratin 14 and collagen Ⅰ were detected by Western blot.Results The scratch healing rates of HaCaT-blank group,HaCaT-control group and HaCaT-experimental group were(21.05±1.10)％,(22.33±1.72)％and(41.61±2.90)％;the cell migration numbers were 57.00±11.36,60.38±10.11 and 287.75±20.21,respectively.The scratch healing rates of HSF-blank group,HSF-control group and HSF-experimental group were(17.82±1.62)％,(19.81±3.87)％and(64.22±1.94)％,the cell migration numbers were 43.25±7.98,40.75±6.70 and 140.88±14.35,respectively.The HaCaT-experimental group was compared with HaCaT-blank group and HaCaT-control group,and the HSF-experimental group was compared with HSF-blank group and HSF-control group,the differences were statistically significant(all P＜0.05).The protein expression levels of β-catenin in the model group,experimental-L,-H groups were 0.53±0.06,0.74±0.17 and 1.44±0.11;the protein expression levels of keratin 14 were 0.33±0.06,0.54±0.07 and 1.26±0.16;the protein expression levels of PCNA were 0.46±0.05,0.72±0.09 and 1.14±0.11;the protein levels of collagen Ⅰ were 0.52±0.03,0.77±0.05 and 1.28±0.13,respectively.There were significant differences in the above indexes between the experimental-L,-H groups and the model group(P＜0.05,P＜0.01).Conclusion Hesperidin may promote the healing of acute skin wounds in mice by activating the Wnt/β-catenin signaling pathway and increasing the migration of HaCaT and HSF.

【Objective】 To explore the optimal parameters for detecting mitochondrial respiratory function (MRF) in apheresis platelets (AP) using real-time energy metabolism detection technology, and to study the change of MRF in AP during storage. 【Methods】 AP samples were collected and detected for MRF using the Seahorse XF device. Multiple parameters such as AP loading concentrations, washing conditions and mitochondrial respiratory regulatory drug concentrations were adjusted. Finally, the MRF in AP stored for 1 and 5 days were studied. 【Results】 The optimal parameters for detecting MRF in AP were as follows: The loading concentration was 5×10⁷/100 μL and basal respiration was 316±65; Basal respiration in washing group was 329±120 compared with 57±7 in unwashing group; The concentration of FCCP was 2 μmol/L. The basal respiration in AP for 1 day was 683±161, while was 140±23 for 5 days, P<0.05; The maximum respiration in AP for 1 day was 1 044±82, while was less than 200 for 5 days, P<0.05. There was a significant difference in MRF dynamic curves between the two groups. 【Conclusion】 The real-time energy metabolism detection technology was able to detect MRF in AP effectively. The MRF significantly damaged during AP storage, indicating that it may be one new mechanism of platelet storage lesion.